본문 바로가기
KERD
논문KCI 등재

17Beta-Estradiol Inhibits Calcium-Activated Potassium Channel Expressions in Rat Whole Bladder

1

조회

0

다운로드

0

인용

0

참고문헌

키워드

초록

Purpose: To investigate the effect of estrogen on the expression of calcium-activated potassium (KCa) channels in an overactive bladder rat model. To this end, mRNA and protein levels of KCa channel subtypes in the bladder of ovariectomized rats were measured by reverse transcription polymerase chain reaction and western blotting, respectively. Methods: Ten-week-old female Sprague-Dawley rats were divided randomly into 3 groups: sham-operated control group (n=11), ovariectomy group (n=11), and the group treated with estrogen after ovariectomy (n=12). Rats in the last group were subcutaneously injected with 17β-estradiol (50 μg/kg) every other day for 2 weeks, whereas rats in the other 2 groups received vehicle (soybean oil) alone. Two weeks after treatment, the whole bladder was excised for mRNA and protein measurements. Results: Protein levels of the large-conductance KCa (BK) channels in the ovariectomy group were 1.5 folds higher than those in the sham-operated control group. However, the protein levels of the other KCa channel subtypes did not change significantly upon bilateral ovariectomy. Treatment with 17β-estradiol after ovariectomy restored BK channel protein levels to the control value. In contrast, BK channel mRNA levels were not significantly affected by either ovariectomy alone or 17β-estradiol treatment. The small-conductance KCa type 3 channel (SK3) mRNA and protein levels decreased to 75% of control levels upon 17β-estradiol treatment. Conclusions: These results suggest that 17β-estradiol may influence urinary bladder function by modulating BK and SK3 channel expression.

Abstract

Purpose: To investigate the effect of estrogen on the expression of calcium-activated potassium (KCa) channels in an overactive bladder rat model. To this end, mRNA and protein levels of KCa channel subtypes in the bladder of ovariectomized rats were measured by reverse transcription polymerase chain reaction and western blotting, respectively. Methods: Ten-week-old female Sprague-Dawley rats were divided randomly into 3 groups: sham-operated control group (n=11), ovariectomy group (n=11), and the group treated with estrogen after ovariectomy (n=12). Rats in the last group were subcutaneously injected with 17β-estradiol (50 μg/kg) every other day for 2 weeks, whereas rats in the other 2 groups received vehicle (soybean oil) alone. Two weeks after treatment, the whole bladder was excised for mRNA and protein measurements. Results: Protein levels of the large-conductance KCa (BK) channels in the ovariectomy group were 1.5 folds higher than those in the sham-operated control group. However, the protein levels of the other KCa channel subtypes did not change significantly upon bilateral ovariectomy. Treatment with 17β-estradiol after ovariectomy restored BK channel protein levels to the control value. In contrast, BK channel mRNA levels were not significantly affected by either ovariectomy alone or 17β-estradiol treatment. The small-conductance KCa type 3 channel (SK3) mRNA and protein levels decreased to 75% of control levels upon 17β-estradiol treatment. Conclusions: These results suggest that 17β-estradiol may influence urinary bladder function by modulating BK and SK3 channel expression.

참고문헌 (35)

  1. Tomaszewski J, "Postmenopausal overactive bladder", Prz Menopauzalny, 13, pp.313~329 (2014)
  2. Turpen HC, "Mirabegron: a new option in treating overactive bladder", JAAPA, 28, pp.16~18 (2015)
  3. Andersson KE, "New developments in the management of overactive bladder: focus on mirabegron and onabotulinumtoxinA", Ther Clin Risk Manag, 9, pp.161~170 (2013)
  4. Robinson D, "Estrogens and the lower urinary tract", Neurourol Urodyn, 30, pp.754~757 (2011)
  5. Rahn DD, "Vaginal estrogen use in postmenopausal women with pelvic floor disorders: systematic review and practice guidelines", Int Urogynecol J, 26, pp.3~13 (2015)
  6. Tseng LH, "Randomized comparison of tolterodine with vaginal estrogen cream versus tolterodine alone for the treatment of postmenopausal women with overactive bladder syndrome", Neurourol Urodyn, 28, pp.47~51 (2009)
  7. Petkov GV, "Beta1-subunit of the Ca2+-activated K+ channel regulates contractile activity of mouse urinary bladder smooth muscle", J Physiol, 537(Pt 2), pp.443~452 (2001)
  8. Chen M, "Identification of large conductance calcium activated potassium channel accessory beta4 subunit in rat and mouse bladder smooth muscle", J Urol, 182, pp.374~381 (2009)
  9. Hristov KL, "Largeconductance voltage- and Ca2+-activated K+ channels regulate human detrusor smooth muscle function", Am J Physiol Cell Physiol, 301, pp.C903~C912 (2011)
  10. Malysz J, "Single-channel biophysical and pharmacological characterizations of native human large-conductance calcium-activated potassium channels in freshly isolated detrusor smooth muscle cells", Pflugers Arch, 465, pp.965~975 (2013)
  11. Petkov GV, "Central role of the BK channel in urinary bladder smooth muscle physiology and pathophysiology", Am J Physiol Regul Integr Comp Physiol, 307, pp.R571~R584 (2014)
  12. Zhu N, "Alternative splicing of Slo channel gene programmed by estrogen, progesterone and pregnancy", FEBS Lett, 579, pp.4856~4860 (2005)
  13. Yasay GD, "Mechanoinhibitory effect of estradiol in guinea pig urinary bladder smooth muscles", Pharmacology, 51, pp.273~280 (1995)
  14. Song M, "Hormonal control of protein expression and mRNA levels of the MaxiK channel alpha subunit in myometrium", FEBS Lett, 460, pp.427~432 (1999)
  15. Nagar D, "Estrogen regulates {beta}1-subunit expression in Ca(2+)-activated K(+) channels in arteries from reproductive tissues", Am J Physiol Heart Circ Physiol, 289, pp.H1417~H1427 (2005)
  16. Afeli SA, "SK but not IK channels regulate human detrusor smooth muscle spontaneous and nerve-evoked contractions", Am J Physiol Renal Physiol, 303, pp.F559~F568 (2012)
  17. Sales S, "Effects of 17beta-estradiol replacement on the apoptotic effects caused by ovariectomy in the rat hippocampus", Life Sci, 86, pp.832~838 (2010)
  18. Rozen S, "Primer3 on the WWW for general users and for biologist programmers", Methods Mol Biol, 132, pp.365~386 (2000)
  19. Muller YL, "Regulation of Ca2+-dependent K+ channel expression in rat cerebellum during postnatal development", J Neurosci, 18, pp.16~25 (1998)
  20. Wang W, "Properties and expression of Ca2+-activated K+ channels in H9c2 cells derived from rat ventricle", Am J Physiol, 276(5 Pt 2), pp.H1559~H1566 (1999)
  21. Etiz Sayharman S, "Effects of combined estrogen and progesterone replacement treatment on detrusor contractility and histology in oophorectomized rats", J Obstet Gynaecol Res, 37, pp.1638~1644 (2011)
  22. Tsang SY, "Differential regulation of K+ and Ca2+ channel gene expression by chronic treatment with estrogen and tamoxifen in rat aorta", Eur J Pharmacol, 483, pp.155~162 (2004)
  23. Vasudevan S, "Switching from repression to activation:microRNAs can up-regulate translation", Science, 318, pp.1931~1934 (2007)
  24. Klinge CM, "miRNAs regulated by estrogens, tamoxifen, and endocrine disruptors and their downstream gene targets", Mol Cell Endocrinol, 418(Pt 3), pp.273~297 (2015)
  25. Pietrzykowski AZ, "Posttranscriptional regulation of BK channel splice variant stability by miR-9 underlies neuroadaptation to alcohol", Neuron, 59, pp.274~287 (2008)
  26. Fang D, "17β-estradiol regulates cell proliferation, colony formation, migration, invasion and promotes apoptosis by upregulating miR-9 and thus degrades MALAT-1 in osteosarcoma cell MG-63 in an estrogen receptor-independent manner", Biochem Biophys Res Commun, 457, pp.500~506 (2015)
  27. Eghbali M, "Diminished surface clustering and increased perinuclear accumulation of large conductance Ca2+-activated K+ channel in mouse myometrium with pregnancy", J Biol Chem, 278, pp.45311~45317 (2003)
  28. Valverde MA, "Acute activation of Maxi-K channels (hSlo) by estradiol binding to the beta subunit", Science, 285, pp.1929~1931 (1999)
  29. Brenner R, "BK channel beta4 subunit reduces dentate gyrus excitability and protects against temporal lobe seizures", Nat Neurosci, 8, pp.1752~1759 (2005)
  30. Wang B, "Mechanism of beta4 subunit modulation of BK channels", J Gen Physiol, 127, pp.449~465 (2006)
  31. Yan J, "BK potassium channel modulation by leucine-rich repeat-containing proteins", Proc Natl Acad Sci U S A, 109, pp.7917~7922 (2012)
  32. Parajuli SP, "NS309decreases rat detrusor smooth muscle membrane potential and phasic contractions by activating SK3 channels", Br J Pharmacol, 168, pp.1611~1625 (2013)
  33. Ikeda Y, "Role of gap junctions in spontaneous activity of the rat bladder", Am J Physiol Renal Physiol, 293, pp.F1018~F1025 (2007)
  34. Kim SJ, "Therapeutic effects of connexin inhibitors on detrusor overactivity induced by bladder outlet obstruction in rats", Urology, 78, pp.475.e1~475.e7 (2011)
  35. Babaoglu M, "Gap junction expression and the effects of gap junction inhibitors in overactive bladder models: does ovariectomy have a role?", Int Urol Nephrol, 45, pp.1001~1008 (2013)

관련 논문AI추천

Effects of Estrogens on the Expression of Caveolin-1 in the Urinary Bladders of Female Rats권동득, 김선옥, 김형석, 송승희, 오경진, 이승철, 조경아, 황의창, 황인상대한배뇨장애요실금학회 · International Neurourology Journal2011 · 제15권 제1호The Expression of AQP1 and eNOS in Menopausal Rat Urinary Bladder권동득, 김동희, 김선옥, 류수방, 박광성, 송승희, 안규윤, 황의창대한배뇨장애요실금학회 · International Neurourology Journal2010 · 제14권 제2호Distribution of Interstitial Cells of Cajal in Menopausal Rat Urinary Bladder Showing Detrusor Overactivity권동득, 김선옥, 송승희, 안규윤대한배뇨장애요실금학회 · International Neurourology Journal2010 · 제14권 제1호Decreased Expression of Urethral Caveolin-1, -2, and -3 in the Rat Model of Overactive Bladder: Potential Mediator of Functional Interaction of Urethra and Urinary Bladder김선옥, 조현진, Han-Yi Jiao대한배뇨장애요실금학회 · International Neurourology Journal2023 · 제27권 제1호Overexpression of Aquaporin-1 and Caveolin-1 in the Rat Urinary Bladder Urothelium Following Bladder Outlet Obstruction권동득, 김선옥, 박광성, 송승희대한배뇨장애요실금학회 · International Neurourology Journal2013 · 제17권 제4호난소절제술 후 암컷 백서 방광의 생리적, 형태학적 변화 및 호르몬 보충요법길건, 구대용, 김강섭, 김진겸, 나용길, 설종구, 신주현, 임재성대한배뇨장애요실금학회 · International Neurourology Journal2007 · 제11권 제2호

이 간행물의 다른 논문 (24건)